From: Super-enhancers: critical roles and therapeutic targets in hematologic malignancies
Disease | Combination | Effect | Reference |
---|---|---|---|
Lymphoma | OTX015, mTOR inhibitor everolimus, BTK inhibitors ibrutinib, HDAC inhibitor vorinostat, and anti-CD20 monoclonal antibody rituximab | Synergic anti-lymphoma activity in vitro and in vivo | Boi M, et al [154]; Gaudio E, et al [155]. |
Diffuse large B cell lymphoma cell lines and xenograft mouse model | |||
Activated B-cell-like (ABC) DLBCL cells and xenograft mouse model | JQ1, BTK kinase inhibitor rbrutinib | Reduce IκB kinase activity and inhibit cells proliferation | Ceribelli M, et al [151] |
Lymphoma-derived cell lines | BAY 1238097, EZH2 inhibitor DZNep, GSK-126, everolimus and ibrutinib | Synergistic cytotoxicity in vitro | Bernasconi E, et al [156] |
B- cell lymphoma xenograft mouse model | RVX2135, ATR inhibitor AZ20 | Enhanced sensitivity to ATR inhibitor in vitro and in mouse models of B-cell lymphoma, and improve survival | Muralidharan, et al. |
Myc-transgenic mice lymphoma models | RVX2135, HDAC inhibitor panobinostat, vorinostat | Inhibit proliferation and induce apoptosis of lymphoma cells | Bhadury, et al [141] |
Human lymphoma B-cell lines | JQ1, rituximab | JQ1 Increase Rituximab sensitivity in lymphoma cells with CYCLON and MYC expression | Emadali A, et al [152] |
Primary effusion lymphoma (PEL) cell lines and orthotopic xenograft model | JQ1, lenalidomide | Synergistic cytotoxicity in PEL cell lines an increased the survival of PEL bearing NOD–SCID mice | Gopalakrishnan, et al [157] |
Mantle cell lymphoma cell lines and mice models | CPI203, lenalidomide | Synergistic antitumor activity in bortezomib-resistant mantle cell lymphoma | Moros A, et al [153] |
Leukemia | JQ1, cytarabine (ARA-C) | Synergistic anti-leukemic effects | Herrmann H, et al [146] |
Acute myeloid leukemia (AML) cell lines HL60 and KG1 | |||
Patient-derived AML cells and mice model | JQ1, JAKi ruxolitinib, HSP90i AUY922 | Inhibit growth and induce apoptosis of patient-derived AML cells, and improved survival of mice engrafted with AML cells; Enhanced sensitivity to ruxolitinib-resistant AML cells. | Saenz DT, et al [158] |
 AML cell lines, primary patient samples, and xenograft models | BI 894999, CDK9 Inhibitors flavopiridol, LDC000067 | Synergistic antitumor effects and lead to rapid induction of apoptosis in vitro and in vivo. | Gerlach D, et al [101] |
AML cells expressing FLT3-ITD and TKI-resistant cell lines | JQ1, FLT3 inhibitor ponatinib, AC220, panobinostat | Inhibit growth and induce apoptosis of human AMLÂ cells; Synergistic induction of apoptosis in TKI-resistant cells | Fiskus W, et al [140] |
AML xenograft mouse model | ABBV-075, Bcl-2 inhibitor venetoclax, hypomethylating agent azacitadine, proteasome inhibitor bortezomib | augments the activities of venetoclax, azacitidine, in xenograft models of AML. | Bui MH, et al [144] |
Human AML xenograft models | INCB054329 and LSD1 Inhibitor INCB059872 | Enhanced myeloid differentiation and apoptosis in human AML cell lines | Liu X, et al [145] |
Human T-cell acute lymphoblastic leukemia (T-ALL)Â cells | JQ1 and CK2 inhibitor CX-4945 | Induce apoptosis in human T-ALL cells, | Lian H, et al [149] |
Primary Acute lymphoblastic leukaemia (ALL) cases, ALL cell lines and ALL xenograft models | JQ1 and dexamethasone | JQ1 sensitized ALL cells to dexamethasone, and reduced subcutaneous tumor growth in ALL xenograft models. | Da Costa D, et al [147] |
Myeloma | INCB054329 and JAK inhibitors (ruxolitinib or itacitinib) | Inhibit myeloma cell growth in vitro and in vivo | Stubbs MC, et al [102] |
 Multiple myeloma (MM) models | |||
In vitro and in vivo models of MM | CPI203 and lenalidomide/dexamethasone | Improve therapy response in relapsed/refractory patients with MM | DÃaz T, et al [159] |
bortezomib and melphalan resistant MM cell lines and patients sample | CPI203 and bortezomib | enhanced apoptosis and anti-proliferative effects | Siegel M B, et al [160] |